What is the mechanism of action of this treatment?

The most common treatments for melanoma, particularly advanced cases, include immunotherapies such as checkpoint inhibitors (e.g., nivolumab, pembrolizumab) and personalized vaccines like NeoVax. Checkpoint inhibitors work by blocking proteins that prevent T-cells from attacking cancer cells, thereby enhancing the immune response against melanoma. NeoVax, a personalized neoantigen vaccine, stimulates the immune system to recognize and target specific mutations unique to an individual's tumor. This personalized approach can lead to a more effective and targeted immune response, potentially improving outcomes for melanoma patients by reducing tumor growth and spread.

What side effects are associated with this type of intervention?

Common treatments for melanoma, particularly immunotherapies like nivolumab and pembrolizumab, can cause a range of immune-related adverse events (irAEs). These include fatigue, rash, diarrhea, and endocrine disorders such as hypothyroidism. More severe but less frequent side effects can involve inflammation of the lungs (pneumonitis), colon (colitis), liver (hepatitis), and kidneys (nephritis). These side effects are typically manageable with corticosteroids and other immunosuppressive treatments.

What prior FDA approvals exist?

The FDA has approved several immunotherapies for the treatment of melanoma, particularly immune checkpoint inhibitors such as pembrolizumab (Keytruda) and nivolumab (Opdivo). These drugs work by blocking proteins that prevent the immune system from attacking melanoma cells. Additionally, ipilimumab (Yervoy), another checkpoint inhibitor, has been approved for melanoma treatment. While personalized neoantigen vaccines like NeoVax are still under investigation, these approved therapies represent significant advancements in leveraging the immune system to combat melanoma.

What other types of research exist?

Promising novel alternatives to NeoVax for melanoma patients include: 1) Adjuvant nivolumab plus ipilimumab or nivolumab alone, which has shown efficacy in resected stage IV melanoma with no evidence of disease. 2) Personalized neoantigen-pulsed dendritic cell vaccines, which have demonstrated superior immunogenicity and anti-tumor effects in preclinical models. 3) Combination therapies involving NeoVax with CDX-301 and immune checkpoint inhibitors like nivolumab or pembrolizumab, which are currently being studied for their potential to enhance immune responses and improve clinical outcomes.

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Cancer Vaccine

NeoVax + CDX-301 + Nivolumab for Melanoma

Phase 1

Recruiting

Led By Patrick A Ott, MD, PhD

Research Sponsored by Dana-Farber Cancer Institute

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Participants must have histologically confirmed stage IIIB/C/D or stage IV cutaneous melanoma (mucosal melanoma or uveal melanoma are excluded) that is surgically resected, is deemed surgically resectable, or is unresectable; tumor tissue for sequence analysis must be available from either previous melanoma resection/biopsy or at least one site of disease must be amenable to surgical or core biopsy

Creatinine ≤ 1.5 x ULN OR Creatinine clearance ≥40 mL/min/1.73 m2 for participants with creatinine levels above institutional normal

Must not have

Test positive for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection

Pregnant women are excluded from this study because Nivolumab, personalized neoantigen peptides and poly-ICLC are agents with unknown risks to the developing fetus. Because there is an unknown but potential risk of adverse events in nursing infants secondary to treatment of the mother with Nivolumab, personalized neoantigen peptides and poly-ICLC, nursing women are excluded from this study

Timeline

Screening 3 weeks

Treatment Varies

Follow Up toxicities experienced within 49 days/7 weeks of neoantigen vaccine treatment initiation

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a personalized vaccine called NeoVax, combined with other drugs, to treat melanoma. The vaccine is made from the patient's own tumor proteins to help the immune system fight cancer. The study aims to find a safe way to use these treatments together and determine the right dose.

Who is the study for?

Adults with stage IIIB/C/D or IV melanoma that's resectable or unresected, and not mucosal/uveal type. Must have good performance status, normal organ/marrow function, no severe allergies to study drugs, no HIV/AIDS or hepatitis B/C infection. Women must test negative for pregnancy and agree to contraception; men also need to use contraception.

What is being tested?

The trial is testing a combination of NeoVax (a personalized cancer vaccine), CDX-301, and Nivolumab against melanoma. Participants will receive these drugs to see if they work better together in treating the disease compared to current standard treatments.

What are the potential side effects?

Possible side effects include reactions at the injection site from the vaccine, flu-like symptoms such as fever and chills, fatigue, skin reactions like rash or itching. Nivolumab can cause immune-related issues affecting organs like lungs or intestines.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My melanoma is confirmed, operable or not, and tissue is available for testing.

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My kidney function is within the required range.

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I am fully active or can carry out light work.

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I am 18 years old or older.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have tested positive for hepatitis B or C.

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I am not pregnant or breastfeeding.

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I am not planning any major surgery, except possibly for melanoma removal.

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I haven't taken any cancer drugs or immunosuppressants in the last 6 months.

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I haven't taken high-dose steroids or immunosuppressants in the last 14 days.

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I am allergic to Nivolumab or CDX-301.

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I have active cancer spread to my brain or its coverings.

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I do not have any ongoing serious illnesses or infections.

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My cancer has Flt-3 mutations.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ toxicities experienced within 49 days/7 weeks of neoantigen vaccine treatment initiation

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~toxicities experienced within 49 days/7 weeks of neoantigen vaccine treatment initiation

This trial's timeline: 3 weeks for screening, Varies for treatment, and toxicities experienced within 49 days/7 weeks of neoantigen vaccine treatment initiation for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Rate of Dose Limiting Toxicity (DLT)

Recommended maximum tolerated dose (MTD)

Secondary study objectives

Estimate rates of disease progression/recurrence depending on whether patient had all melanoma resected or has measurable disease per RECIST 1.1

Neoantigen-specific cellular immune responses

Side effects data

From 2024 Phase 3 trial • 529 Patients • NCT02017717

80%

Fatigue

70%

Diarrhoea

70%

Headache

40%

Vomiting

40%

Aspartate aminotransferase increased

40%

Rash maculo-papular

40%

Alanine aminotransferase increased

40%

Lipase increased

30%

Partial seizures

30%

Hemiparesis

30%

Gait disturbance

30%

Fall

30%

Cough

30%

Dry skin

30%

Amylase increased

30%

Nausea

30%

Confusional state

20%

Malignant neoplasm progression

20%

Pyrexia

20%

Candida infection

20%

Mucosal infection

20%

Decreased appetite

20%

Back pain

20%

Dysphonia

20%

Hypotension

20%

Colitis

20%

Hyperthyroidism

20%

Oedema peripheral

20%

Muscular weakness

20%

Hypothyroidism

10%

Tinnitus

10%

Cushingoid

10%

Diabetic ketoacidosis

10%

Procedural haemorrhage

10%

Blood bilirubin increased

10%

Bradycardia

10%

Sinus tachycardia

10%

Hyperglycaemia

10%

Hypocalcaemia

10%

Neck pain

10%

Brain oedema

10%

Hydrocephalus

10%

Lethargy

10%

Seizure

10%

Hypertension

10%

Palpitations

10%

Cheilitis

10%

Presyncope

10%

Face oedema

10%

Oedema

10%

Conjunctivitis

10%

Enterocolitis infectious

10%

Oral candidiasis

10%

Pneumonia

10%

Sinusitis

10%

Staphylococcal infection

10%

Blood alkaline phosphatase increased

10%

Spinal pain

10%

Tremor

10%

Dizziness

10%

Dysarthria

10%

Urinary retention

10%

Dyspnoea exertional

10%

Nasal congestion

10%

Pneumonitis

10%

Dermatitis

10%

Erythema

10%

Rash

10%

Klebsiella infection

10%

Hypomagnesaemia

10%

Syncope

10%

Haemorrhage intracranial

10%

Pancreatitis

10%

Cholecystitis

10%

Upper respiratory tract infection

10%

Acute kidney injury

10%

Dermatitis bullous

10%

Lymphopenia

10%

Optic nerve disorder

10%

Visual impairment

10%

Dehydration

10%

Hypokalaemia

10%

Scoliosis

10%

Cognitive disorder

10%

Memory impairment

10%

Hallucination

10%

Insomnia

10%

Irritability

10%

Urinary incontinence

10%

Dyspnoea

10%

Dermatitis acneiform

10%

Pelvic venous thrombosis

10%

Sepsis

100%

80%

60%

40%

20%

Study treatment Arm

Cohort 1: Arm N1+I3

Cohort 2: Arm B

Part A Cohort 1c: Arm N3+RT+TMZ

Part A Cohort 1d: Arm N3+RT

Part B Cohort 1c: Arm N3+RT+TMZ

Part B Cohort 1d: Arm N3+RT

Cohort 1: Arm N3

Cohort 1b: Arm N3+I1

Cohort 2: Arm N3

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Group I: CDX-301 + Neovax + PembrolizumabExperimental Treatment3 Interventions

* Participants will have vaccine made from tissue collected from tumor biopsy, or from previously collected archival biopsy or surgical tissue. * Participants will receive neoadjuvant Pembrolizumab for 3 doses every 3 weeks, then undergo standard-of-care surgical resection. * Participants will receive adjuvant NeoVax and CDX-301. CDX-301 will be administered at a predetermined dose, dependent on the number of participants previously enrolled, for 5 days starting 2 days before the initiation of NeoVax. CDX-301 will then be administered at a predetermined dose dependent on the number of participants previously enrolled 2 days before and for 5 days coinciding with the administration of NeoVax on days 50 and 78. * Participants will receive adjuvant Pembrolizumab for 15 doses every 6 weeks.

Group II: CDX-301 + Neovax + NivolumabExperimental Treatment3 Interventions

* Participants will have vaccine made from tissue collected from metastatic tumor biopsy or surgical resection, or from previously collected archival biopsy or surgical tissue. * Participants will receive Nivolumab at a flat dose every 4 weeks up to two years. * Participants will receive CDX-301 at a predetermined dose dependent on the number of participants previously enrolled for 5 days starting 2 days before the initiation of NeoVax. CDX-301 will then be administered at a predetermined dose dependent on the number of participants previously enrolled 2 days before and for 5 days coinciding with the administration of NeoVax on days 50 and 78.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Pembrolizumab

2017

Completed Phase 3

~3150

CDX-301

2017

Completed Phase 1

~170

Nivolumab

2015

Completed Phase 3

~4010

0 / 13Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for melanoma, particularly advanced cases, include immunotherapies such as checkpoint inhibitors (e.g., nivolumab, pembrolizumab) and personalized vaccines like NeoVax. Checkpoint inhibitors work by blocking proteins that prevent T-cells from attacking cancer cells, thereby enhancing the immune response against melanoma. NeoVax, a personalized neoantigen vaccine, stimulates the immune system to recognize and target specific mutations unique to an individual's tumor. This personalized approach can lead to a more effective and targeted immune response, potentially improving outcomes for melanoma patients by reducing tumor growth and spread.